The response from researchers worldwide to the growing pandemic in 2020 was extremely rapid and supported by the European Union with funding initiatives such as the H2020-SC1-PHE-CORONAVIRUS-2020 call.
One of these is Exscalate4Cov (“EXaSCale smArt pLatform Against paThogEns for Corona Virus”), which combines the expertise of research labs across Europe with supercomputer facilities in Italy, Spain and Germany. The project started on April 2020 with 18 partners from all over Europe. The initiative is centred around a virtual screening infrastructure based on the LiGen™ software, owned by Dompe’ (an italian biopharmaceutical company) but has been co-developed with CINECA and other partners over the last 15 years.
The computational pipeline of the project involves running very long molecular dynamics simulations of viral proteins with the GROMACS software. The outputs are then used as targets in the virtual screening procedure of Ligen. The software components have been optimized to make very efficient use of both Cineca’s M100 supercomputer and the HPC5 system of Eni S.p.A. Therefore, we can perform very long 10 microsecond molecular dynamics simulations in a few months and docking runs capable of processing millions of molecules a second.
An outcome of the docking experiments using a database of compounds known to be safe for humans (i.e. either known drug molecules or from natural products) has been the identification of a set of molecules with a potential inhibitory effect on virus replication. Laboratory experiments confirmed the inhibition influence of some of these and one compound in particular, the osteoporosis drug Raloxifene, was selected for application to the European Medicines Agency (EMA). The application was successful and is currently in a clinical trial in Italy. Subsequently, a further two compounds have been identified and are awaiting approval from the EMA as clinical candidates.
Exscalate4Cov has been remarkably successful, with over a trillion potential drug molecules and 45 proteins simulated and has made all the data generated within the project freely available outside the consortium, either directly from open-source repositories or via the associated partners programme. So far, the project is generating valuable data: more than 400 active molecules have been identified so far out of >30000 experimental data generated, and 29 peer review papers.
